1. Field of Art
Hantaviruses
Hantaviruses are a group of at least 19 diverse agents. They occur worldwide in rodent hosts and cause either (1) no known human disease; (2) hemorrhagic fever with renal syndrome, HFRS, or (3) Hantavirus pulmonary syndrome (HPS) when transmitted to man. The following is a compilation of currently recognized types; there is not universal agreement among workers in the field as to the degree to which each is clearly distinct from each other:
Since there are so many distinct species of Hantaviruses, there is no single test or single reagent that allows the diagnosis of all hantavirus infection. In each case, the best reagents for detection of antibodies to a given hantavirus are those which are based upon the hantavirus species that actually caused the infection. The nucleocapsid (N) protein is the portion of each hantavirus that is most strongly immunogenic, and the standard for diagnosis of Hantaviruses has increasingly been to rely upon the expression of homologous N protein in bacteria or other microbial expression system to generate high concentrations of recombinant-expressed antigen. Classical methods of viral antibody detection have depended upon the growth of the virus in culture, with use of the viral antigens from infected cultures in immunologic detection, but these methods are increasingly falling out of favor for a variety of technical and practical reasons.
2. Discussion of Related Art
Specific diagnostic tests are available for several previously-described Hantaviruses. For Hantaviruses in general, antibody tests are much preferred over direct detection of infectious viral particles, viral genomic RNA, or viral antigens because of the inherently superior stability, sensitivity, specificity, and ease of transfer of antibody assay technologies. The following modalities are in common use (C) or are under development or research use (D) for the following Hantaviruses:
Because none of the prototype Hantaviruses listed above occurs in rodents with distribution in South America, it is virtually certain that human Hantavirus disease in South America is due to novel virus(es) that will be detected in a less-than-optimal manner by tests that utilize antigens derived from prototype species. These virus(es) are almost certainly associated with indigenous rodents of the subfamily Sigmodontinae, family Muridae, because the clinical disease that has been noted in Brazilian, Argentinean, and Paraguayan patents is closely similar to those diseases caused by North American Hantaviruses of sigmodontine rodents. Detection of Hantavirus infection in South America has relied most heavily upon cross-reactivity between the prototypic sigmodontine rodent-borne Hantavirus Sin Nombre (Four Corners) virus (SNV) and the South American virus(es).
The invention provides a molecular clone encoding and expressing the complete nucleotide protein of Rio Mamorxc3xa9 virus. The RMV N protein includes antigenically active domains useful in immunoassays for detecting South American Hantavirus infection, and in vaccines.